title: Pectenotoxin-2 induces G1 arrest of the cell cycle in synovial fibroblasts of patients with rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA), a chronic inflammatory disease, is characterized by hyperplasia of the synovial fibroblasts, due in part to increased cell growth. This study investigated the mechanisms underlying the anti-proliferative action of pectenotoxin-2 (PTX-2), isolated from marine sponges, in synovial fibroblasts obtained from RA patients. PTX-2 concentration-dependently inhibited the growth of synovial fibroblasts, arresting them in the G1 phase of their cell cycle. The G1 arrest was correlated with down-regulation of cyclin D1 and cyclin-dependent kinase (Cdk) 6, with a concomitant up-regulation of the tumor suppressor, p53, and the Cdk inhibitor, p21 (WAF1/CIP1). Following PTX-2 treatment of synovial fibroblasts, an increased binding of p21 with Cdk2 and Cdk6 was paralleled by a significant decrease in retinoblastoma protein (pRB) phosphorylation and in the protein levels of E2F transcription factors. Thus, PTX-2 might help identify new therapeutic agents against RA-mediated hyperplasia of synovial fibroblasts.
authors.affiliation: Blue-Bio Industry Regional Innovation Center, Dongeui University, Busan, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Jee Hyung
authors.initials: JH
authors.lastname: Jung
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002455:Cell Division; D049109:Cell Proliferation; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005663:Furans / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D018942:Macrolides; D010766:Phosphorylation; D011714:Pyrans / Q000494:pharmacology*; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism; D000095702:Polyether Toxins
chemical_list: D018501:Antirheumatic Agents; D051357:Cyclin-Dependent Kinase 2; D051361:Cyclin-Dependent Kinase 6; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005663:Furans; D018942:Macrolides; D011714:Pyrans; C098380:pectenotoxin 2; D000095702:Polyether Toxins; C495894:CDK2 protein, human